Over the past years the Division of Oncology at the University of Washington has been involved in a continuing program of marrow transplantation for the treatment of patients with advanced, otherwise fatal malignant and non-malignant hemopoietic diseases. A number of grafted patients have become long-term survivors without recurrence of their original disease and without occurrence of graft-versus-host disease. Many patients, however, have died from recurrent disease or, more frequently, from complications related to the transplant. Further improvement in clinical marrow grafting hinges upon progress in and better understanding of at least three major areas of study: 1) recovery of immunologic reactivity in marrow graft recipients, 2) understanding of mechanisms of stable graft-host tolerance and of graft-versus-host disease, 3) methods of recognizing and overcoming sensitization of a marrow graft recipient by preceding blood transfusions. It is the objective of this proposal to conduct an immunologic investigation into those three areas of study.